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W Sauermann

Publications and source records attributed to W Sauermann.

At least 19 recordsLinked to original sources
PubMed1997

The slope parameter of concentration-response curves used as a touchstone for the existence of spare receptors.

The present work was stimulated by findings of a large reserve of presynaptic alpha2-autoreceptors in rat neocortex by different investigators and our own group, using classical models of receptor agonism. The mathematical background of these classical models seems erroneous since the asymmetry that spare receptors introduce into concentration-response curves is not considered appropriately. This asymmetry leads to a steepening of curve fits based on the logistic function. Therefore, the slope parameter c of a logistically fitted concentration-response curve can be used as a touchstone for the existence of spare receptors. Spare receptors induce a c > 1. Concentration-response data of the alpha2-autoreceptor-mediated inhibition of evoked [3H]-noradrenaline release in rat neocortex slices were re-analysed. The estimates of the slope parameter c of logistically fitted concentration-response curves obtained after treatment of rats with either vehicle or N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to achieve an irreversible inactivation of alpha2-autoreceptors, were not compatible with the existence of a large receptor reserve. A model for nonlinear regression analysis developed under the a priori assumption of spare receptors confirmed the absence of spare receptors. Evaluation methods which neglect the alteration of the geometrical form of concentration-response curves due to non-proportionality between receptor occupation and relative response do not seem appropriate to quantify spare receptors. These methods may detect spare receptors where they do not exist.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

Gabapentin in generalized seizures.

The efficacy of gabapentin (Neurontin), in generalized seizures was evaluated in this 14 week, double-blind, placebo-controlled, parallel-group, add-on, multicenter study. A total of 129 patients with refractory generalized seizures were randomized to receive either placebo or 1200 mg/day gabapentin as add-on therapy. Patients received their standard regimens of antiepileptic drugs (AEDs) during a 12 week baseline period, and gabapentin or placebo was added-on in the subsequent 14 week evaluation period. Results of both an intent-to-treat (ITT) and evaluable-patient analyses showed that gabapentin provided greater reduction in the frequency of generalized tonic-clonic seizures than did placebo; however, the differences between treatments were not statistically significant. Gabapentin did not affect the frequency of absence or myoclonic seizures. Adverse events were reported by 67% of gabapentin-treated patients and by 56% of placebo-treated patients. The most frequently occurring adverse events among patients receiving gabapentin were somnolence, fatigue, and dizziness. Gabapentin is well tolerated by patients with generalized seizures. The results of this study show a trend toward an effect of gabapentin in reducing the frequency of generalized tonic-clonic seizures and suggest that further exploration of high dose gabapentin in generalized epilepsy is warranted.

Acetates↗
PubMed1995

Direct molecular analysis of myotonic dystrophy in the German population: important considerations in genetic counselling.

Myotonic dystrophy (DM) is associated with the expansion and instability of a trinucleotide (CTG) repeat at the DM locus on chromosome 19. Direct genomic analysis in the German population was carried out on 18 DM families, six families with equivocal diagnosis, 69 subjects with equivocal clinical diagnosis, and 100 controls using the polymerase chain reaction (PCR) and a refined Southern protocol. In the majority of the cases molecular analysis confirmed the clinical diagnosis. These included seven cases of congenital DM (CDM) with widely differing gene expansions and instabilities. In most DM families the expanded fragment became larger in successive generations, but we also identified four families with contractions and two families that showed stability of the enlarged fragment during transmission. In four clinically defined DM patients we were unable to detect enlarged CTG repeats. Sequencing of each exon of the DM gene in two of these patients failed to show any mutations. Our cases have important implications for genetic counselling of DM families, highlighting both the diagnostic value of direct genomic analysis and its limitations.

Adult↗
PubMed1994

The antiparkinsonian drugs budipine and biperiden are use-dependent (uncompetitive) NMDA receptor antagonists.

N-Methyl-D-aspartate- (NMDA-) evoked [3H]acetylcholine release in rabbit caudate nucleus slices was inhibited by the antiparkinsonian drugs budipine (1-tert-butyl-4,4-diphenylpiperidine) and biperiden (1-bicyclo[2.2.1.]hept-5-en-2-yl-1-phenyl-3-piperidino propanol) yielding functional Ki values of 4.6 and 8.8 microM. In contrast to the competitive antagonist 2-amino-5-phosphonopentaonate, budipine and biperidene significantly reduced both the apparent KD and the Emax value of NMDA. Moreover, they displaced [3H]MK-801 specifically bound to membranes of the same tissue, although with low affinity (IC50: 38 and 92 microM). It is concluded that budipine and biperiden are use-dependent (uncompetitive) antagonists at the NMDA receptor, binding to the receptor-linked ion channel, but probably not to the MK-801 binding site. NMDA antagonism may contribute to the antiparkinsonian effects of budipine.

Acetylcholine↗
PubMed1994

New insights into receptor theory, as provided by an artificial partial agonist made-to-measure.

In the present study a mixture of a full agonist (noradrenaline) and a full antagonist (yohimbine) was used to mimic the effects of a partial agonist (clonidine) on alpha 2-autoreceptor-mediated regulation of noradrenaline release in order to learn more about the shape of concentration-response curves in the absence and presence of spare receptors. The sigmoidal shape of the cloud of single experimental data points may be reflected by different curve fits based on either descriptive or mechanistic mathematical models. Only mechanistic models allow the interpretation of the relationship between occupancy of receptors and induced response. The experiments were performed in rat neocortex and in rabbit hippocampus tissue where electrical field stimulation with 4 pulses/100 Hz of slices prelabelled with [3H]noradrenaline elicited the release of noradrenaline. A receptor reserve was found in the rabbit hippocampus and quantified from the concentration-response curve of noradrenaline in this tissue using a mechanistic general response function, developed to reflect the condition of spare receptors. The mixture of noradrenaline and yohimbine, NA-Yoh, (three parts to one part), corrected by the different affinities to the alpha 2-autoreceptors, was designed to mirror the quantified proportion of 75% non-spare and 25% spare alpha 2-autoreceptors. In the spare receptor-free rat cortex NA-Yoh acted like a typical partial agonist, as clonidine, with nearly the same EC50 (= Kd in this case) as the full agonist noradrenaline, but with a maximum effect significantly lower than that of noradrenaline. In the rabbit hippocampus, however, the same maximum effect was obtained with NA-Yoh, noradrenaline and clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Mathematical modelling and quantification of the autoinhibitory feedback control of noradrenaline release in brain slices.

Concentration-response curves, reflecting alpha 2-autoreceptor-mediated inhibition of [3H]-noradrenaline release by exogenous noradrenaline in rat cerebral cortex and rabbit hippocampus slices, were analysed in order to test the usefulness of a mathematical model describing the relation between the independent variable, exogenous noradrenaline, and the dependent variable, inhibition of release. This model was based on the assumption of direct proportionality between receptor occupation and response, implying that there is correspondence between the shape of a concentration-binding curve and a concentration-response curve. The experimental concentration-response curves were obtained by different approaches: noradrenaline release from brain slices prelabelled with [3H]-noradrenaline was elicited electrically either by pseudo-one-pulse (POP) stimulation or by stimulation with 36 pulses applied with a frequency of 3 Hz. POP stimulation avoids autoinhibition by released noradrenaline and, therefore, was a suitable touchstone for the applied mathematical model which evaluates by nonlinear regression analysis two primary parameters: the dissociation constant between noradrenaline and the alpha 2-adrenoceptor and the biophase concentration of noradrenaline which reflects the extent of autoinhibition and should be zero under POP conditions. In rat cerebral cortex tissue, the corresponding biophase concentration of endogenous noradrenaline was indeed estimated to be zero and the dissociation constant was Kd = 10(-7.62 +/- 0.14) mol/l. With 3 Hz stimulation, the biophase concentration was 10(-7.80 +/- 0.05) mol/l, which has to be interpreted with respect to a simultaneously estimated Kd of 10(-7.63 +/- 0.12) mol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The autoinhibitory feedback control of acetylcholine release in human neocortex tissue.

Slices of human neocortex prelabelled with [3H]choline were superfused and stimulated electrically (3 Hz, 2 ms, 24 mA) in order to investigate the autoreceptor-mediated modulation of acetylcholine (ACh) release. The concentration-response curve of the muscarinic agonist oxotremorine (pKd = 6.76 +/- 0.06), which was equipotent to ACh, was shifted to the right in a parallel manner by atropine (pA2 = 8.56 +/- 0.11), as evaluated by non-linear regression analysis. Calculation of the biophase concentration of ACh showed that no ACh could be assumed to be present under these conditions, whereas following inhibition of the acetylcholinesterase by physostigmine (0.1 microM) a biophase concentration of 10(-6.89 +/- 0.11) M was estimated. The depression of ACh release due to physostigmine and tacrine, another anticholinesterase, was antagonized by atropine. When the autoinhibition was operative atropine and the M2 subtype specific muscarinic antagonists, AF-DX 116 and methoctramine, significantly increased the release of ACh whereas the 'facilitatory' effects of the M1 and M3-specific drugs, pirenzepine and hexahydrosiladifenidol, were not significant. Although different disinhibitory effects of the subtype-specific antagonists were found, they did, however, not show a pattern which would allow a clear characterisation of the subtype of muscarinic receptor associated with the autoreceptor. The release of ACh from neocortex tissue of the (non-demented) neurosurgical patients decreased with their age. This finding is consistent with the hypothesis that the normal aging process resembles a delayed and attenuated disease process of senile dementia of Alzheimer's type.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

The conditions of Ca2+ entry via L-type channels for induction of serotonin release from rabbit hippocampus.

The L-type voltage-sensitive calcium channel (VSCC) agonists of the dihydropyridine (DHP) type, Bay K 8644 and (+)-202-791, concentration dependently enhanced the K+ (26.2 mM)-induced 5-HT release from slices of rabbit hippocampus prelabelled with [3H]5-HT when the slices were treated with the monoamine oxidase (MAO) inhibitor, pargyline. The DHP agonists were ineffective on K+ (26.2 mM)-induced release in the absence of pargyline. However, when omega-conotoxin GVIA pretreatment of the slices irreversibly blocked N-type VSCCs, (+)-202-791 markedly enhanced the release of 5-HT evoked by 26.2 mM K+. Thus, at this rather strong stimulus intensity either an increase in the (preferentially cytoplasmic) transmitter pool or blockade of N-type VSCCs was necessary in order to unmask agonist-activated L-type VSCCs. Reduction of the depolarization intensity from 26.2 to 17.2 mM K+, given for 8 min, strongly intensified the stimulatory effects of L-type VSCC agonists irrespective of the use of pargyline under these conditions. The concentration-response curve of (+)-202-791 was 'competitively' shifted to the right by the enantiomer, (-)-202-791, with a pA2 value of 8.6. In conclusion, N- and L-type VSCCs seem to differ in their relation to the cellular machinery for 5-HT release, the latter getting markedly operative when a weak and sustained depolarization is applied or when N-type VSCCs are blocked or when the cytoplasmic transmitter pool is expanded by inhibition of MAO.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

[Multiple sclerosis with early manifestation in children].

From the starting point of cases reported in literature, five of the authors' own cases are reported in which multiple sclerosis had its origins not later than in the fourteenth year of the patient's life. There is no basic difference from adult cases in respect of neurological symptoms, course, and cerebrospinal-fluid condition, but unmistakably, well remitting episodic courses were in the foreground, multilocular failures preponderated, and cerebral symptoms predominated over spinal symptoms. As in adult cases, females were more commonly affected. There were inflammatory changes in the cerebrospinal fluid.

Adolescent↗
PubMed1986

[Epileptic seizures in multiple sclerosis].

Starting from informations in the literature, the authors deals with eight own cases, suffering from clinically certain multiple sclerosis and showing, as a further sign, epileptic seizures. Compared to the total of patients, these eight cases represent 1.78 p.c. of all patients treated for multiple sclerosis in this clinic. The features of seizures, frequency and dynamics of occurrence are referred to. The authors point out that it is necessary to differential between epileptic seizures and non-epileptic attacks, and they draw attention to the fact that here are difficulties with regard to differential diagnosis if epileptic seizure appears as a initial symptom of multiple sclerosis.

Adult↗
PubMed1983

[EDP (electronic data processing)-oriented special documentation in neurology--extension to a computer epicrisis].

The contribution describes a final neurological documentation system for in-patients that permits the computerized print-out of an epicrisis. The computer automatically summarizes the elementary findings and presents them as a number of important neurological syndromes. The structure of the documentation and the experience gained in the course of many years of routine application are described. The system has proved to be basically sound under the conditions existing at a university hospital and a specialized hospital for psychiatry and neurology and has proved applicable for a large proportion of the patients without major restrictions.

Aftercare↗
PubMed1983

[Electronic data processing-compatible documentation in neurology--developmental stage of neurologic findings for a specialty-specific scientific evaluation system and print-out of a computer assisted epicrisis].

A computer compatible neurological examination record has been drawn up for a neurological documentation called "ADOK Neurologie" as part of a scheme for the basic registration of patient-related information from all patients receiving ward treatment at the Medical Academy Dresden and the County Neurological and Psychiatric Hospital Arnsdorf. The examination questionnaire consists of dichotomous questions and permits up to 1,525 separate items of neurological information per patient to be stored and processed. The information permits purposeful scientific analysis and computer print-out of the epicrisis. The article reports on the structure of the questionnaire, the prospects and limits of the method and experience gained during many years of practical use.

Computers↗
PubMed1983

[Guillain-Barré polyradiculitis in acute viral hepatitis type B--case report].

A polyneuritis of the Guillain-Barré type developed in a 29 year-old female patient during the icteric stage of viral hepatitis B. The main symptoms were diffuse paresthesias and increasing motor weakness of the limbs, ending up in paralysis of the legs. The analysis of the CSF (albumin raised, cell count normal) and electroneurographic findings were diagnostically reaffirming. The patient was given prednisolone. All symptoms disappeared within two months.

Acute Disease↗
PubMed1981

[Further experiences with the Imurek treatment in multiple sclerosis].

A report is given on 82 patients suffering from multiple sclerosis (MS) who were treated over a period of up to a maximum of eight years - average treatment 4-6 years. The best results were found in patients passing through an acute episode. Among the chronic-progressive cases, 5.1 per cent of the patients showed an improvement. In 24.4 per cent of the cases the clinical picture remained unchanged. 64.1 per cent showed a deterioration. Side-effects were gastric complaints, considerable leucocyte depression, oedemas, loss of hair, strumata, increase in transaminases, recrudescence of mycosis and pyoderma. In one case a state of confusion was observed. - Special criteria for the Imurek treatment are recommended. The necessity of a closed-meshed supervision of the patients is pointed out.

Azathioprine↗
PubMed1979

[Diagnostic problems of chronic misuse of barbiturate-free sedatives].

Atypical neuropsychiatric disease pictures resulting from chronic abuse of barbiturate-free soporifics are often misinterpreted diagnostically. The problems of diagnosis are discussed on the basis of experience gathered by the authors and with due consideration of results reported in the literature.

Diagnosis, Differential↗
PubMed1976

[Preliminary results of imurek treatment of multiple sclerosis].

The authors, after presenting a survey of the literature on the treatment of multiple sclerosis with immunosuppressants, report their experience with Imurek. Of 53 patients with a chronic and progressive course of the disease, objective improvement could be observed in 17. In 20 patients the symptomatology remained unchanged, although 4 of them reported subjective improvement. In 16 patients, progression of the disease could not be stopped. Better results of treatment could be obtained for those forms of the disease where the course was, first, in the form of what may be referred to as outbursts and, later, in a chronic and progressive form. -Possible side effects are pointed out.

Adult↗